The possibility of producing and purifying large quantities of recombinant rotavirus VP4 from insect cell cultures was investigated. Spodoptera frugiperda (Sf9) cells were grown in large spinner flasks and infected with a baculovirus expressing the rotavirus OSU VP4 gene. The expressed VP4 subsequently was purified from such cultures to determine the yield of recombinant protein. Conditions for growth of cells and high yield of VP4 were optimized to improve the expression of VP4. Also, a practical purification scheme was developed to maximize the yield of VP4 from insect cell cultures and to reduce cost and complexity of a potential industrial-scale purification process.